Wilms Tumor

Background

Wilms tumor is an intrarenal tumor of neoplastic embryonal renal cells of the metanephros.

Most common malignant renal tumor of childhood (6% of all childhood cancers)

450 to 500 cases of Wilms tumor diagnosed in the United States annually (an incidence of 8 cases per million in children under 15 years of age)

Median age at diagnosis of Wilms tumor is about 3 years of age, with earlier diagnosis occurring in bilateral tumors. The incidence of bilateral tumors is 7%.

2/3 of cases are diagnosed before the age of 5 and 95% of cases before the age of 10

Occurs with equal frequency in males and females, with a slightly higher incidence of disease in African American children than in Caucasian and Asian children

Most develop sporadically, 10% of cases are associated with recognized syndromes

Common Symptoms

Abdominal or flank mass, may be unilateral or bilateral, generally smooth and firm

Typically asymptomatic, may cause abdominal pain, found in nearly half of patients, due to hemorrhage into the tumor or invasion of the renal pelvis

Hematuria, often microscopic

Hypertension, found in up to 25% of patients at presentation. Possible etiologies include: renin production by the tumor, renal ischemia secondary to invasion into the renal artery, or intraparenchymal AV fistula formation.

Diagnosis

When an abdominal mass is discovered, the initial imaging modality of choice is ultrasound.

Essential prior to treatment to accurately localize the source of the mass, identify any genitourinary abnormalities that may co-exist, and to examine the contralateral kidney.

Intrarenal masses are suggestive of Wilms tumor; extrarenal masses suggest another cause, such as a neuroblastoma.

CT is often the next imaging modality of choice, which can confirm the location and extent of the tumor, assess the vena cava, and evaluate the contralateral kidney.

Chest radiograph is also performed in order to rule out pulmonary metastases, as up to 15% of patients will have pulmonary metastases at the time of diagnosis.

Differential Diagnosis Abdominal/Pelvic Tumors

Neuroblastoma: will usually have increased urinary metanephrines (VMA, HVA)

NHL: Increased LDH, bone marrow infiltration

Rhabdomyosarcoma: present in a wider range of ages, can affect the urogenital system and may present with vaginal bleeding or paratesticular mass

Prognosis

Continued screening for pulmonary spread by serial chest CT and for development in the contralateral kidney by serial ultrasound

Associated Anomalies

Wilms tumor is associated with a number of congenital anomalies and syndromes:

WAGR syndrome — Wilms tumor, Aniridia, Genital anomalies, and mental Retardation. This syndrome is associated with a constitutional deletion on chromosome 11 (del 11p13 — the WT1 locus), and the incidence of Wilms tumor in this syndrome is over 40%.

Beckwith-Weideman syndrome — an overgrowth syndrome characterized by excess growth at the cellular, tissue and organ levels. It is associated with organomegaly, macroglossia, hypoglycemia, omphalocele and hemihypertrophy. Beckwith-Weideman syndrome is caused by a change in the gene locus at band p15.5 on chromosome 11 — the WT2 locus. The risk of Wilms tumor with Beckwith-Weideman syndrome is from 10 to 20%.

Denys-Drash syndrome — a very rare syndrome of male pseudohermaphroditism (or genitourinary abnormalities), renal mesangial sclerosis and Wilms tumor. The genetic abnormality in these infants also maps to chromosome 11, p13, but it is a dominant negative, missense mutation.

Aniridia — children with sporadic aniridia are at risk for Wilms tumor. The incidence of aniridia in patients with Wilms tumor is 1.1%.

Children with horseshoe kidney are at twice the risk of developing Wilms tumor when compared to the general population.

Screening Recommendations

Children diagnosised with Beckwith-Wiedemann or WAGR syndromes

Unaffectd kidney of children with previously diagnosed unilateral tumor (1.5% of children diagnosed with Wilms' before the age of one will develop a second tumor in the remaining unaffected kidney)